Serial evaluation of cardioprotective effects of exercise training in heart failure using cardiac diffusion tensor MRI

使用心脏扩散张量 MRI 连续评估运动训练对心力衰竭的心脏保护作用

• 批准号: 10672834
• 负责人: Christopher T Nguyen
• 金额: $ 43.73万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-11-04 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10672834
• 关键词: 3-Dimensional; Address; Aerobic; Affect; Agreement; Architecture; Biological Markers; Biopsy; Blood; Bone Marrow; Cardiac; Cardiac Myocytes; Cell Therapy; Cessation of life; Clinical; Consensus; Consequentialism; Data; Detection; Diffusion; Diffusion Magnetic Resonance Imaging; Dose; Echocardiography; Effectiveness; Electrocardiogram; Evaluation; Exercise; Exercise Therapy; Exhibits; Family suidae; Fiber; Financial compensation; Fluorescence Microscopy; Genetic Transcription; Gold; Heart failure; Histology; Imaging Techniques; Incidence; Individual; MRI Scans; Magnetic Resonance Imaging; Measures; Methodology; Methods; Monitor; Motion; Mus; Myocardial; Myocardial Infarction; Myocardium; Outcome; Pacemakers; Patients; Pattern; Pharmaceutical Preparations; Prevalence; Prognostic Marker; Property; RNA marker; Reproducibility; Research; Sampling; Scanning; Signal Pathway; Slice; Structure; Tachycardia; Techniques; Technology; Testing; Therapeutic; Therapeutic Effect; Time; Tissues; Translating; Treatment outcome; United States; cardioprotection; clinical translation; clinically translatable; cohort; coronary fibrosis; denoising deep learning; design; effective therapy; exercise training; functional loss; heart function; imaging modality; improved; improved outcome; in vivo; innovation; insight; multitask; new technology; non-invasive imaging; non-invasive monitor; novel; pre-clinical; preclinical study; preservation; prognostic tool; prognostic value; reconstruction; sedentary; therapeutic evaluation; tomography; tool

Project Summary / Abstract Heart failure (HF) is accounts for 1 in 9 deaths in the United States and currently affects ~6 million with a prevalence of 250,00-400,000 and incidence of 70,000-120,000. Current therapy does not address the underlying loss of functional heart muscle and adverse structural remodeling. One novel potential treatment of HF is exercise (aerobic) therapy that has demonstrated various cardioprotective properties to halt and potentially reverse adverse structural remodeling. However, dosing of exercise therapy remains a challenge due to each individual's inherent differences and consequentially, serial non-invasive monitoring of the therapy would be necessary to evaluate the change on structural remodeling. Furthermore, current non-invasive technologies characterize structural remodeling with surrogate measures and thus, there is no consensus on a single clinical gold-standard. Without a tool to monitor and characterize the degree of structural remodeling, the evaluation of the therapeutic potential of exercise therapy in HF patients cannot be fully realized representing an unmet need in ultimately improving therapy. The proposed project aims to improve the therapy monitoring of exercise training to cardioprotect against HF by revealing its effect on microstructural remodeling with cardiac diffusion tensor MRI (DT-MRI). DT-MRI is a unique, non-invasive technology capable of characterizing myocardial fiber orientation and directly reflecting microstructural remodeling. However, despite major advances, there are fundamental challenges that limit the capability of current cardiac DT-MRI methods to be applied robustly in a clinical setting. In this project, an innovative 5-min “push button” DT-MRI method will be developed that overcomes such limitations. We also leverage institutional strengths to further quantify the accuracy of in vivo DT-MRI in revealing myocardial microstructure using novel tissue cleared 3D histology. The central hypothesis is that addressing these major technical challenges will allow for clinical translation of cardiac DT-MRI to serve as a tool to monitor the therapeutic effects of HF on microstructural remodeling. This is achieved by extending previously developed technologies used for myocardial fibrosis detection with diffusion-weighted MRI. The proposed project is designed to systematically develop an innovative and robust clinical DT-MRI methodology and rigorously validate in a pre-clinical setting the effects of exercise therapy on the microstructural remodeling of HF thereby laying the groundwork for potential optimization of dosing exercise therapy.

项目概要/摘要 在美国，心力衰竭 (HF) 占死亡人数的九分之一，目前影响约 600 万人 患病率为 250,00-400,000，发病率为 70,000-120,000。目前的治疗无法解决这一问题。 潜在的功能性心肌丧失和不良的结构重塑。 心力衰竭是一种运动（有氧）疗法，已证明具有多种心脏保护特性，可阻止和潜在 然而，由于每种原因，运动疗法的剂量仍然是一个挑战。 个体的固有差异，因此，治疗的连续非侵入性监测将是 此外，还需要评估当前的非侵入性技术的变化。 用替代措施来表征结构重塑，因此，对于单一的临床并没有达成共识 如果没有工具来监测和表征结构重塑的程度，就无法评估 运动疗法对心力衰竭患者的治疗潜力无法完全实现，代表需求未得到满足 最终改善治疗。拟议的项目旨在改善运动训练的治疗监测。 通过心脏弥散张量揭示其对微结构重塑的影响来预防心力衰竭 MRI (DT-MRI) DT-MRI 是一种独特的非侵入性技术，能够表征心肌纤维。 定向并直接反映微观结构重塑然而，尽管取得了重大进展，但仍有一些进展。 限制当前心脏 DT-MRI 方法在心脏疾病中稳健应用的能力的根本挑战 在该项目中，将开发一种创新的 5 分钟“按钮”DT-MRI 方法。 我们还利用机构优势进一步量化体内的准确性。 DT-MRI 使用新颖的组织清晰的 3D 组织学揭示心肌微观结构的中心假设。 解决这些主要技术挑战将使心脏 DT-MRI 的临床转化能够服务于 作为监测高频对微结构重塑治疗效果的工具，这是通过扩展来实现的。 先前开发的技术用于通过弥散加权 MRI 检测心肌纤维化。 拟议项目旨在系统地开发创新且稳健的临床 DT-MRI 方法 并在临床前环境中严格验证运动疗法对微观结构重塑的影响 从而为运动疗法剂量的潜在优化奠定了基础。